[source]
pmid = PMID:29174093
title = Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and cutaneous mastocytosis: Clinical report and literature review
[diagnosis]
disease_id = OMIM:616973
disease_label = Intellectual developmental disorder, autosomal dominant 42
[text]
The female proband was born to a nonconsanguineous healthy 40-year-old mother and a healthy 50-year-old father.
No family history of note or exposure to teratogens was reported. The proband has two healthy half-brothers.
She was born by cesarean section at 39 weeks gestation. Apgar scores were 8 and 9 after 1 and 3 min respectively.
Birthweight was 2520 g (5th centile), length 53 cm (95th centile) and occipito-frontal circumference (OFC) 33 cm (15th centile).
No congenital anomalies or dysmorphic features were noted at birth except microretrognathia.
Standard intracranial US revealed slightly increased right ventricle.
Although there were no feeding difficulties or slowing of physical growth within the first year of life,
the achievement of major milestones was severely delayed when assessed for both gross and fine motor, speech, and
social skills development (Table 1). Early neurological assessment revealed muscular hypotonia and extrapyramidal
symptoms (upper-limb choreoathetosis).
Features of cutaneous mastocytosis have been evident in the proband since the end of the first year of life (Fig. 1).
The diagnosis of urticaria pigmentosa form was confirmed by skin biopsy.
Currently, at 4 years, the proband's weight is 14.8 kg (25th-50th centile), height 105 cm (50th-75th centile) and
OFC 48.5 cm (10th-25th centile). She is globally developmentally delayed, although no formal psychological
assessment has been performed yet. She understands simple commands and can speak a few words which seems to
be her biggest challenge. Eye contact is weak. The gait is unstable and wide-based and when walking she
tends to lean forward as if her movements were deconstructed. Generalized hypotonia requires her to prop up when standing up.
The upper and lower limb reflexes are normal. The hand stereotypies (frequent hand-to-mouth movements)
that add to an already existent extrapyramidal upper-limb activity are present. She also has bruxism,
hypermobile tongue and apparently is unable to chew solid foods. The proband has bilateral severe vesicoureteral
reflux that has already required unilateral nephrectomy. Subclinical hypothyroidism has been diagnosed as well.
No significant behavioral abnormalities have been recorded in the proband. Discrete dysmorphic features such as
prominent eyebrows and eyelashes, bilateral fifth finger clinodactyly (present in the relatives on the maternal side) and
unilateral partial skin syndactyly of second and third toes are present.

 In EEG generalized bursts of sharp and slow wave complexes were present but these did not require antiepileptic medication. MRI of the head performed twice was normal as were metabolic studies (TANDEM Mass Spectrometry and Gas Chromatography).